Differential diagnosis of Zika, Chikungunya and Dengue by high resolution and ion mobility mass spectrometry

Abstract

Zika, Chikungunya and Dengue virus have been a major public health challenge in Brazil due to climatic conditions favorable to the dissemination of the mosquito vector Aedes aegypti and its difficult control. The reappearance of Dengue, the sudden epidemic of Zika and Chikungunya, coupled with the large number of underreporting, inaccurate and false diagnoses have placed diagnostic methodologies as one of the central aspects of arboviruses research. The infection caused by the Zika, Chikungunya and Dengue virus requires rapid and reliable diagnosis for the integrated activities of monitoring, suppression and prevention of transmission by the insect vector. Current diagnostic tests of the Zika virus, for example, have several limitations. Serological tests based on immunological reactions have low specificity and sensitivity. Molecular tests are effective in detecting RNA of the virus, but only in the short time after infection. Thus, the metabolomics-based methods for detecting biomarkers of the virus or their interaction with the host appear as complementary tools for diagnosis, since they are discriminatory and can detect co-infections. The metabolomics-based methods allow the detection of physiological variations at all stages of the infection, the immunological responses and the resulting clinical modifications. High resolution mass spectrometry (HRMS) is the most used technique in metabolomics studies for the identification and characterization of biomarkers from various diseases as well as viral infections. The use of techniques and methods of mass spectrometry in the health area has increased in the last decades due to: (i) high sensitivity and specificity that allow obtaining reliable results in a short time; (ii) simplicity of execution of the analysis that is easily performed after standardization of the methodology, and can be automated; (iii) the high initial cost of the equipment can be quickly recovered due to the low cost of the analyzes and very high frequency of analysis. Recently, Ion Mobility Mass Spectrometry (IM-MS) technique has received great attention because of its high capacity to separate isobaric ions (of same m/z) that are not solved by high performance liquid chromatography, as well as the isomers ions. Therefore, the metabolomics-based in high resolution mass spectrometry have great potential to contribute to the search for specific biomarkers of the Zika, Chikungunya and Dengue virus infections, besides making possible the differential diagnosis of these arboviruses, closer to the actual clinical state of the patient, through quantification of biomarkers. (AU)